Biomedical subjects

H H Suh

Publications and source records attributed to H H Suh.

At least 37 records · Page 2Linked to original sources

PubMed1993

Use of personal measurements for ozone exposure assessment: a pilot study.

During summer 1991, we collected indoor, outdoor, and personal ozone concentration data as well as time-activity data in State College, Pennsylvania. These concentrations were measured for 23 children and their homes using passive ozone samplers. Outdoor concentrations were also measured at a stationary ambient monitoring site. Results from this pilot study demonstrate that fixed-site ambient measurements may not adequately represent individual exposures. Outdoor ozone concentrations showed substantial spatial variation between rural and residential regions. Ignoring this spatial variation by using fixed-site measurements to estimate personal exposures can result in an error as high as 127%. In addition, evidence from our pilot study indicates that ozone concentrations of a single indoor microenvironment may not represent those of other indoor microenvironments. Personal exposures were significantly correlated with both indoor (r = 0.55) and outdoor (r = 0.41) concentrations measured at home sites. Multiple regression analyses identified indoor ozone concentrations as the most important predictors of personal exposures. However, models based on time-weighted indoor and outdoor concentrations explained only 40% of the variability in personal exposures. When the model included observations for only those participants who spent the majority of their day in or near their homes, an R2 of 0.76 resulted when estimates were regressed on measured personal exposures. It is evident that contributions from diverse indoor and outdoor microenvironments must be considered to estimate personal ozone exposures accurately.

Air Pollution, Indoor↗

PubMed1992

Different radiant heat intensities differentiate intracerebroventricular morphine- from beta-endorphin-induced inhibition of the tail-flick response in the mouse.

The antinociceptive effects of morphine and beta-endorphin given intracerebroventricularly (i.c.v.) or intrathecally (i.t.) were evaluated by inhibition of the tail-flick and hot-plate paw-licking responses evoked by three different intensities of heat stimulation (low, intermediate and high) in male ICR mice. Morphine given i.c.v. was more potent in inhibiting the tail-flick response evoked by low than high intensity of heat stimulus. beta-Endorphin given i.c.v., on the other hand, was equally potent in inhibiting the tail-flick response evoked by different intensities of heat. This differential effect of morphine and beta-endorphin was not shown when morphine and beta-endorphin were given i.t. Morphine and beta-endorphin given i.c.v. or i.t. were equally potent in inhibiting the paw-licking response at different intensities of hot-plate temperature. Our results suggest that morphine given i.c.v. may inhibit high intensity heat-evoked tail-flick response spinally and inhibits low intensity heat-evoked tail-flick response supraspinally. Our results also provide additional evidence for different neural mechanisms of antinociceptive action of morphine and beta-endorphin.

Analgesia↗

PubMed1992

Intrathecal cholecystokinin octapeptide attenuates the antinociception and release of immunoreactive Met-enkephalin induced by intraventricular beta-endorphin in the rat.

The effects of cholecystokinin octapeptide (CCK8s) given intrathecally (i.t.) on antinociception and the release of immunoreactive Met-enkephalin in the spinal perfusate induced by intraventricular (i.vt.) injection of beta-endorphin were studied in anesthetized rats. beta-Endorphin (5 micrograms) given i.vt. inhibited the tail-flick response. The inhibition of the tail-flick response induced by beta-endorphin was blocked dose-dependently by CCK8s (0.1-7 micrograms) given i.t. The antagonistic effect of CCK8s on beta-endorphin-induced inhibition was blocked dose dependently by co-intrathecal injection of proglumide (3 and 10 micrograms), a CCK8s receptor antagonist. beta-Endorphin (5 micrograms) given i.vt. elicited a release of immunoreactive Met-enkephalin in the spinal perfusate. Repeated injections of the same dose of beta-endorphin released about the same amount of the immunoreactive Met-enkephalin in the spinal perfusate. CCK8s at concentrations from 1 x 10(-9) to 1 x 10(-6) M added into the spinal perfusate decreased the release of Met-enkephalin induced by beta-endorphin given i.vt. in a dose-dependent manner. The results suggest that CCK8s may attenuate beta-endorphin-induced inhibition of the tail-flick response by inhibiting the release of Met-enkephalin from the spinal cord.

Animals↗

PubMed1992

Effects of [Sar1]angiotensin II on proenkephalin gene expression and secretion of [Met5]enkephalin in bovine adrenal medullary chromaffin cells.

We have studied the effect of [Sar1]angiotensin II [S1-AII; a degradation-resistant analogue of angiotensin II (AII) on the release of [Met5]enkephalin (ME) and proenkephalin A (proENK) gene expression. Short-term (15-min to 1-h) stimulation of bovine adrenal medullary chromaffin (BAMC) cells with S1-AII at concentrations from 0.1 to 100 nM had no significant effect on secretion of ME, whereas high concentrations of S1-AII (3 to 100 microM) produced a concentration-dependent increase in the concentration of ME in the incubation media. In contrast, long-term (3- to 24-h) stimulation with low concentrations (0.1 nM-1 microM) of S1-AII increased the secretion of ME in a concentration-dependent manner (EC50 = 1 nM). The intracellular level of ME was not changed by long-term treatment with S1-AII (100 nM). In addition to increased ME secretion, long-term (24-h) stimulation with S1-AII increased the expression of proENK mRNA in a concentration-dependent manner (EC50 = 4 nM). Losartan (2-n-butyl-4 chloro-5-hydroxymethyl-1-[(2'-(1 H-tetrazol-5-yl)biphenyl-4-yl)- methyl]imidazole potassium salt, a type 1 AII receptor antagonist) inhibited these effects, whereas PD123319 (50 microM, a type 2 AII receptor antagonist) was inactive. Our results suggest that AII in BAMC cells exerts a major effect on the long-term regulation of expression of proENK mRNA and secretion of ME. These effects appear to be mediated by type 1-like AII receptors.

Adrenal Medulla↗

PubMed1992

Angiotensin II receptors are coupled to omega-conotoxin-sensitive calcium influx in bovine adrenal medullary chromaffin cells.

The contribution of an omega-conotoxin GVIA (omega Cgtx)-sensitive Ca2+ influx pathway to the effects of angiotensin II (AII) receptor activation was examined in bovine adrenal medullary (BAM) cells. Pretreatment of BAM cells with 10(-6) M omega Cgtx blocked stimulation of exocytosis by the degradation-resistant analogue, sarcosine1-angiotensin II (S1-AII). In contrast, omega Cgtx had no effect on basal secretion, nor did it inhibit [3H]norepinephrine and [32P]ATP release in response to bradykinin, another phospholipase C-linked receptor agonist. Similarly, omega Cgtx pretreatment inhibited the stimulation of 45Ca2+ uptake by S1-AII, but did not affect the response to bradykinin. This selective inhibition did not appear to be due to blockade of AII receptors by omega Cgtx, as the accumulation of 3H-labeled inositol phosphates in response to S1-AII was not inhibited. The peak S1-AII-stimulated increase in the intracellular free Ca2+ concentration (Cai) in fura 2-loaded BAM cells also was not significantly reduced by omega Cgtx (or by stimulating in nominally Ca(2+)-free buffer), indicating that this response is dependent on intracellular Ca2+ pools. However, a small omega Cgtx-sensitive Cai response was detected after depletion of intracellular Ca2+ pools with ionomycin. This study shows that AII receptors, but not bradykinin receptors, are linked to an omega Cgtx-sensitive Ca2+ influx pathway in BAM cells.

Adrenal Medulla↗

PubMed1992

Prolonged stimulation of bovine adrenal chromaffin cells with arachidonic acid and prostaglandin E2 increases expression of the proenkephalin gene and the secretion of [Met5]-enkephalin.

The effects of long-term exposure of bovine adrenal medullary chromaffin (BAMC) cells to arachidonic acid (AA) and prostaglandin E2 (PGE2) on [Met5]-enkephalin (ME) secretion and expression of the proenkephalin A (proENK) gene were studied. Treatment with various concentrations of AA or PGE2 for 24 hr increased the secretion of ME in a concentration- and time-dependent manner. At high concentrations (10-100 microM), but not low (1-3 microM), AA significantly increased ME secretion by 1 hr. In contrast, the onset time for increase of ME secretion by PGE2 was 3 hr after exposure. The magnitude of increase in ME secretion in the presence of AA or PGE2 continued to increase with time. However, intracellular ME levels in AA- or PGE2-treated cells were not significantly different from that of controls, indicating that elevated levels of ME secretion into the media may be a result of increased biosynthesis of ME. In addition, AA or PGE2 increased proENK mRNA level in a concentration- and time-dependent manner. The onset time for the increase in proENK mRNA in response to PGE2 was 6 hr after exposure. The treatment of BAMC cells with 20 microM cycloheximide (a protein synthesis inhibitor) inhibited both the increased secretion of ME and proENK mRNA level induced by AA and PGE2 in a time-dependent manner, indicating that the delayed secretion of ME and the increase in proENK mRNA level induced by AA and PGE2 require protein synthesis. Indomethacin (a cyclooxygenase inhibitor, 10 microM) effectively inhibited AA-induced responses, whereas 10 microM nordihydroguaiaretic acid (a lipoxygenase inhibitor) was inactive.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Medulla↗

PubMed1990

Differential effects of sulfated cholecystokinin octapeptide and proglumide injected intrathecally on antinociception induced by beta-endorphin and morphine administered intracerebroventricularly in mice.

The effects of sulfated cholecystokinin octapeptide (CCK-8s) and CCK-8s antagonist, proglumide, given intrathecally (i.t.) on inhibition of the tail-flick and hot-plate paw-licking responses induced by beta-endorphin and morphine given intracerebroventricularly (i.c.v.) were studied in male ICR mice. Both CCK-8s (up to 0.5 ng) and proglumide (up to 10 micrograms) injected alone did not affect significantly the control latencies of the tail-flick and paw-licking responses. I.t. injection of CCK-8s as doses from 0.125 to 0.5 ng dose dependently attenuated inhibition of the tail-flick response induced by i.c.v. administered beta-endorphin. The antagonistic effect of CCK-8s on beta-endorphin-induced inhibition was blocked by the co-i.t. injection of proglumide (0.1-1 micrograms) in a dose-dependent manner. High doses (2.5-10 micrograms) of proglumide given i.t. dose dependently enhanced inhibition of the tail-flick response induced by i.c.v. administered beta-endorphin. However, i.t. injection of CCK-8s and proglumide did not affect inhibition of the paw-licking response induced by i.c.v. administered beta-endorphin. The inhibitions of the tail-flick and paw-licking responses induced by i.c.v. administered morphine were not affected by i.t. injection of CCK-8s or proglumide. Our results suggest that CCK-8s in the spinal cord may play an important modulatory role in attenuating the descending pain inhibition induced by i.c.v. administered beta-endorphin but not morphine.

Analgesics↗

PubMed1990

Different types of opioid receptors mediating analgesia induced by morphine, DAMGO, DPDPE, DADLE and beta-endorphin in mice.

The effects of intracerebroventricular (i.c.v.) administration of D-Phe-Cys-Tyr-D-Try-Orn-Thr-Pen-Thr-NH2 (CTOP), a selective mu-opioid receptor antagonist, (Allyl)2-Tyr-Aib-Aib-Phe-Leu-OH (ICI 174864) and (N,N-Bisallyl-Tyr-Gly-Gly-psi-(CH2S)-Phe-Leu-OH (ICI 154129), selective delta-opioid receptor antagonists on blocking analgesia induced by beta-endorphin, morphine, D-Ala2-NMePhe4-Gly-ol-enkephalin (DAMGO), D-Ala2-D-Leu5-enkephalin (DADLE) and D-Pen2-enkephalin (DPDPE) administered i.c.v. were studied in male ICR mice. The analgesia was assessed by the tail-flick and paw-licking (hot-plate) tests. The potencies of opioid agonists injected i.c.v. for producing analgesia were DAMGO greater than DADLE greater than beta-endorphin greater than morphine greater than DPDPE. Intracerebroventricular administration of CTOP (0.05 micrograms) selectively antagonized inhibition of the tail-flick and paw-licking response induced by morphine, DAMGO or DADLE but not beta-endorphin or DPDPE. ICI 174864 (5 micrograms) and ICI 154129 (5 micrograms) injected i.c.v. selectively antagonized analgesia induced by DPDPE or DADLE but not beta-endorphin, morphine or DAMGO injected i.c.v. These results indicate that analgesia induced by morphine and DAMGO is mediated by the stimulation of mu-opioid receptors while analgesia induced by DPDPE is mediated by the stimulation of delta-opioid receptors. DADLE-induced analgesia is mediated by the stimulation of both mu- and delta-opioid receptors. Analgesia induced by beta-endorphin is mediated by neither mu- nor delta-opioid receptors.

Analgesia↗

PubMed1990

Lack of antinociceptive cross-tolerance between intracerebroventricularly administered beta-endorphin and morphine or DPDPE in mice.

Antinociceptive tolerance and cross-tolerance to intracerebroventricular (i.c.v.) beta-endorphin, morphine, and DPDPE (D-Pen2-D-Pen5-enkephalin) induced by a prior i.c.v. administration of beta-endorphin, morphine and DPDPE, respectively, were studied in mice. Acute tolerance was induced by i.c.v. pretreatment with beta-endorphin (0.58 nmol), morphine (6 nmol) and DPDPE (31 nmol) for 120, 180 and 75 min, respectively. Various doses of beta-endorphin, morphine or DPDPE were then injected. The tail-flick and hot-plate tests were used as antinociceptive tests. Pretreatment of mice with beta-endorphin i.c.v. reduced inhibition of the tail-flick and hot-plate responses to i.c.v. administered beta-endorphin, but not morphine and DPDPE. Pretreatment of mice with morphine i.c.v. reduced inhibition of the tail-flick and hot-plate responses to morphine but not beta-endorphin. Pretreatment of mice with DPDPE reduced inhibition of the tail-flick and hot-plate responses to DPDPE but not beta-endorphin. The results indicate that one injection of beta-endorphin, morphine or DPDPE induces acute antinociceptive tolerance to its own distinctive opioid receptor and does not induce cross-tolerance to other opioid agonists with different opioid receptor specificities. The data support the hypothesis that beta-endorphin, morphine and DPDPE produce antinociception by stimulating specific epsilon, mu- and delta-opioid receptors, respectively.

Analgesics↗

PubMed1990

Intrathecal administration of thiorphan, bestatin, desipramine and fluoxetine differentially potentiate the antinociceptive effects induced by beta-endorphin and morphine, administered intracerebroventricularly.

The effects of the intrathecal injection of thiorphan (an inhibitor of enkephalinase inhibitor), bestatin (an inhibitor of aminopeptidase), desipramine (an inhibitor of the uptake of noradrenaline) and fluoxetine (an inhibitor of the uptake of serotonin) on the antinociception induced by beta-endorphin and morphine, administered intracerebroventricularly, were studied in male ICR mice. Antinociceptive effects were assessed by the tail-flick and hot-plate tests. Thiorphan (16 micrograms) and bestatin (16 micrograms), injected intrathecally, potentiated inhibition of the tail-flick response, induced by beta-endorphin but not by morphine administered intracerebroventricularly, whereas desipramine (6 micrograms) and fluoxetine (6 micrograms), injected intrathecally potentiated inhibition of the tail-flick response induced by morphine, but not by beta-endorphin, administered intracerebroventricularly. Thiorphan, bestatin, desipramine or fluoxetine, given intrathecally, did not antagonize inhibition of the hot-plate response, induced by beta-endorphin or morphine administered intracerebroventricularly. The results indicate that inhibition of the tail-flick response, induced by beta-endorphin administered intracerebroventricularly, is mediated by the opioid system, but not by noradrenergic and serotonergic systems in the spinal cord. On the other hand, the inhibition of the tail-flick response, induced by morphine given intracerebroventricularly, is mediated by noradrenergic and serotonergic systems, but not by the opioid system in the spinal cord. The lack of effect of enzyme inhibitors and inhibitors of the uptake of biogenic amines intrathecally on beta-endorphin- and morphine-induced inhibition of the hot-plate response, is due to the supraspinal nature of the nociceptive hot-plate response. The present results further support the hypothesis, proposed previously, that intracerebroventricularly injected beta-endorphin and morphine elicit antinociception by activating different descending inhibitory systems.

Analgesics↗

PubMed1990

Tolerance to delta- but not mu-opioid receptors in the spinal cord attenuates inhibition of the tail-flick response induced by beta-endorphin administered intracerebroventricularly in mice.

Male ICR mice were rendered tolerant by intrathecal (IT) injection once a day with either mu-agonist, D-Ala2-NMePhe4-Gly-ol-enkephalin (DAMGO) or delta-agonist, D-Pen2-D-Pen5-enkephalin (DPDPE) (toleragen) by doubling the dose each day starting from 0.125 and 1 microgram for DAMGO and DPDPE, respectively, for 6 days. On day 6, the magnitude of tolerance was assessed by establishing IT dose-response lines for the effect of the chronic drug given as bolus injections (probe). The antinociception was assessed by the tail-flick and hot-plate test. Repeated IT injections of DPDPE reduced inhibition of the tail-flick and hot-plate response induced by DPDPE (ED50 values for DPDPE increase 10-fold) but not DAMGO. Repeated IT injections of DAMGO reduced inhibition of the tail-flick and hot-plate response induced by DAMGO (ED50 value for DAMGO increase 7- to 10-fold) but not DPDPE. The effects of the tolerance to mu- and delta-opioid receptor activity in the spinal cord on inhibition of the tail-flick and hot-plate response induced by intracerebroventricularly (ICV) administered beta-endorphin and morphine were then studied. beta-Endorphin or morphine at different doses were injected ICV 4 hr after the last IT injection of DPDPE or DAMGO. Repeated IT bolus injections of DPDPE reduced inhibition of the tail-flick response but not the hot-plate response induced by beta-endorphin. On the other hand, repeated IT bolus injections of DAMGO did not affect inhibition of the tail-flick and hot-plate response induced by beta-endorphin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Intrathecal administration of thiorphan and bestatin enhances the antinociception and release of Met-enkephalin induced by beta-endorphin intraventricularly in anesthetized rats.

Effects of bestatin and thiorphan administered intrathecally, on inhibition of the tail-flick response and the release of Met-enkephalin induced by beta-endorphin administered intraventricularly were studied in anesthetized rats. Intrathecal pretreatment with 100 micrograms of thiorphan or bestatin potentiated the inhibition of the tail-flick response induced by beta-endorphin injected intraventricularly in pentobarbital anesthetized rats; the ED50 values for beta-endorphin were decreased 5- and 7-fold by thiorphan and bestatin, respectively. To determine if the potentiating effect was due to the inhibition of the degradation of Met-enkephalin released by intraventricular beta-endorphin, the effects of intrathecal perfusion with thiorphan or bestatin on the release of immunoreactive Met-enkephalin from the spinal cord by intraventricular injection of beta-endorphin were studied. beta-Endorphin injected into the 4th ventricle at a dose of 5 micrograms increased immunoreactive Met-enkephalin in the spinal perfusate in urethane-anesthetized rats. Thiorphan or bestatin (1 x 10(-7) to 1 x 10(-4) M each) increased the amount of immunoreactive Met-enkephalin released by intraventricular beta-endorphin in a dose-dependent manner. The results provide additional evidence for the hypothesis that antinociception induced by beta-endorphin is mediated by release of Met-enkephalin.

Aminopeptidases↗

PubMed1990

Delta but not mu-opioid receptors in the spinal cord are involved in antinociception induced by beta-endorphin given intracerebroventricularly in mice.

The present studies were designed to determine what type of opioid receptor, mu or delta, in the spinal cord was involved in beta-endorphin-induced antinociception. The tail-flick response was used as an antinociceptive test. Intrathecal (i.t.) injection of ICI-174,864 [(Allyl)2-Tyr-Aib-Aib-Phe-Leu-OH] (10 micrograms) or ICI-154,129 [(N,N-Bisallyl)-Tyr-Gly-Gly-psi-(CH2S)-Phe-Leu-OH] (20 micrograms), delta-opioid receptor antagonists, but not beta-funaltrexamine (0.025 microgram), a mu-opioid receptor antagonist, antagonized inhibition of the tail-flick response induced by beta-endorphin given i.c.v. However, i.t. injection of the same dose of ICI-174,864, ICI-154,129 or beta-funaltrexamine did not affect inhibition of the tail-flick response induced by morphine given i.c.v. Mice were pretreated i.c.v. with either beta-endorphin (2 micrograms), morphine (2 micrograms) or saline (5 microliters) for 2, 3 or 4 hr (which were times that the tail-flick response was no longer inhibited) and were injected i.t. with various doses of D-Ala2-NMePhe4-Gly-ol-enkephalin (a selective mu-opioid receptor agonist), D-Ala2-D-Leu5-enkephalin (a mu- and delta-opioid receptor agonist) or D-Pen2-D-Pen5-enkephalin (a delta-opioid receptor agonists). The tail-flick response was performed 10 min after i.t. injection. A single i.c.v. pretreatment with beta-endorphin for 2 and 3 hr, but not 4 hr, reduced markedly the inhibition of the tail-flick response induced by D-Pen2-D-Pen5-enkephalin and D-Ala2-DLeu5-enkephalin, but not D-Ala2-NMePhe4-Gly-ol-enkephalin, injected i.t.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesia↗

PubMed1989

Intrathecal [Met5]enkephalin antibody blocks analgesia induced by intracerebroventricular beta-endorphin but not morphine in mice.

Intrathecal (i.t.) injection of antibody directed to [Met5]enkephalin antagonized intracerebroventricularly (i.c.v.) administered beta-endorphin-induced inhibition of the tail-flick response but not the hot-plate response. [Met5]enkephalin antibody injected i.t., however, did not affect inhibition of either the tail-flick and hot-plate response induced by morphine given i.c.v. The antibodies to [Leu5]enkephalin, dynorphin A-(1-13) and beta-endorphin even at a high dose injected i.t. did not affect the inhibition induced by i.c.v. administered beta-endorphin or morphine either in the tail-flick and hot-plate test. Our results with antibodies support the results of previous studies that beta-endorphin but not morphine produces its analgesic action by selectively releasing [Met5]enkephalin.

Animals↗

PubMed1989

Differential mechanisms mediating beta-endorphin- and morphine-induced analgesia in mice.

Effects of yohimbine, methysergide and naloxone given intrathecally (i.t.) and naloxone given intracerebroventricularly (i.c.v.) on inhibition of the tail-flick and hot-plate response induced by beta-endorphin and morphine given i.c.v. were studied in male ICR mice. Yohimbine (1.5 and 15 micrograms) and methysergide (1.5 and 15 micrograms) injected i.t. antagonized inhibition of the tail-flick response induced by morphine but not beta-endorphin administered i.c.v. On the other hand, naloxone (20 ng) injected i.t. antagonized inhibition of the tail-flick response induced by i.c.v. administered beta-endorphin but not morphine. Yohimbine and methysergide given i.t. did not antagonize inhibition of the hot-plate response induced by morphine nor did naloxone given i.t. antagonized i.c.v. beta-endorphin-induced inhibition of the hot-plate response. Naloxone given i.c.v. was more effective in antagonizing morphine-induced inhibition of the tail-flick and hot-plate response than inhibition induced by beta-endorphin given i.c.v. Naloxone at doses (0.1 and 1 microgram) which effectively reversed inhibition of the tail-flick response to i.c.v. morphine was not effective in reversing the i.c.v. beta-endorphin-induced inhibition of the tail-flick response. Our results indicate that beta-endorphin and morphine produce analgesia by stimulating separate types of opioid receptors, epsilon- for for beta-endorphin and mu- for morphine, and activate separate descending pain modulatory control systems. The supraspinal epsilon system stimulated by beta-endorphin is mediated by activation of spinal opioid receptors whereas the supraspinal mu system stimulated by morphine is mediated by activation of spinal alpha 2-adrenoceptors and serotonin receptors for the production of analgesia.

Analgesia↗

PubMed1988

Beta-endorphin-(1-27) antagonizes beta-endorphin- but not morphine-, D-Pen2-D-Pen5-enkephalin- and U50, 488H-induced analgesia in mice.

beta-Endorphin-(1-27), administered intraventricularly has been previously reported to block the analgesia induced by beta-endorphin injected intraventricularly. The present study was to determine if the blocking effect of beta-endorphin-(1-27) was specific to beta-endorphin which stimulates epsilon receptors, but not to other opioids with activity at different opioid receptors. The antagonistic effects of beta-endorphin-(1-27) on the analgesia induced by beta-endorphin (epsilon-opioid receptor agonist), D-Ala2-NMePhe4-Gly-ol-enkephalin(DAGO) and morphine, (mu-opioid receptor agonists), D-Pen2-D-Pen5-enkephalin(DPDPE) and D-Ala2-D-Leu5-enkephalin(DADLE) (delta-opioid receptor agonists) and U-50, 488H (kappa-opioid receptor agonist) were studied. beta-Endorphin-(1-27) injected intraventricularly, at doses which, when injected alone did not produce analgesia, antagonized the analgesia induced by beta-endorphin given intraventricularly. However, the analgesia induced by DAGO, morphine, DPDPE, DADLE and U-50, 488H given intraventricularly was not antagonized by beta-endorphin-(1-27). The data suggest that beta-endorphin-(1-27) selectively blocks the analgesia induced by the stimulation of epsilon receptors but not by the stimulation of mu, delta, and kappa receptors. The results support the previously proposed hypothesis that beta-endorphin produces its analgesia by stimulating specific epsilon receptors.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed1988

Intrathecal beta-funaltrexamine antagonizes intracerebroventricular beta-endorphin- but not morphine-induced analgesia in mice.

We have reported previously that beta-endorphin and morphine administered supraspinally produce analgesia by activating different descending pain inhibitory systems in rats. The descending system activated by beta-endorphin involves a spinal endorphinergic system whereas the descending system activated by morphine does not. To determine if this differential action of intraventricular beta-endorphin and morphine also occurs in mice, the effects of pretreatment with intrathecal (i.t.) and i.c.v. beta-funaltrexamine (beta-FNA) on analgesic response induced by i.c.v. and i.t. beta-endorphin and morphine were studied in mice. beta-FNA (2.5 micrograms) was injected i.t. or i.c.v. 24 hr before beta-endorphin or morphine administration and hot-plate and tail-flick responses were measured. Intrathecal beta-FNA attenuated i.c.v. beta-endorphin- but not i.c.v. morphine-induced analgesia. On the other hand, i.t. beta-FNA blocked both i.t. beta-endorphin- and morphine-induced analgesia, but was more effective in blocking the effects of i.t. morphine than beta-endorphin. At the supraspinal sites, beta-FNA administered i.c.v. was found to antagonize i.c.v. morphine-induced analgesia but not i.c.v. beta-endorphin-induced analgesia. The present results in mice are consistent with previous studies in rats and indicate that beta-endorphin and morphine activate different supraspinal opioid receptors. Also, analgesia produced by these two opioids resulted from activation of different descending pain inhibitory systems. The spinal endorphinergic system was involved in the production of i.c.v. beta-endorphin-, but not morphine-induced analgesia.

Analgesia↗

PubMedDate not supplied

Beta-endorphin-(1-27) antagonizes beta-endorphin-induced hypothermia in mice.

The effects of beta-endorphin and beta-endorphin-(1-27) on the body temperature of mice was studied at an ambient temperature of 10 degrees C. Intracerebroventricular injection of beta-endorphin (0.25-4 micrograms) and beta-endorphin-(1-27) (0.61 to 10 micrograms) caused a dose-related hypothermia. The duration of hypothermia induced by beta-endorphin-(1-27) was shorter than that induced by beta-endorphin. The hypothermia induced by 2 micrograms of beta-endorphin was attenuated by 5 micrograms of beta-endorphin-(1-27). Our results indicated that beta-endorphin-(1-27) is a partial agonist which produces a small degree of hypothermia and an antagonist which blocks the beta-endorphin-induced hypothermia.

Animals↗